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Biomedical subjects

A Khan

Publications and source records attributed to A Khan.

At least 523 records · Page 29Linked to original sources

Cisplatin in recurrent pediatric brain tumors. A POG Phase II study. A Pediatric Oncology Group Study.

Forty-six evaluable pediatric patients with primary recurrent brain tumors resistant to standard therapy were treated with cisplatin, 60 mg/m2/day, X2 days every 3 to 4 weeks, to study the efficacy and toxicity of this drug. Complete and partial responses, documented by computed tomography (CT) scan, were demonstrated in 4 of 10 patients with medulloblastoma and 3 of 15 patients with ependymoma. No activity was documented in astrocytic tumors. Dose limiting major toxicities were renal and auditory. It is recommended that the new analogues of cisplatin with less toxicity be studied in these tumors.

Adolescent↗

Cellular origin of human lymphotoxin and its purification.

The ability of various subsets of human mononuclear cells to produce human lymphotoxin (LT) was examined. Peripheral blood mononuclear cells were separated into OKT4+, OKT8+, and Leu-11a+ subpopulations by flow cytometry. Both OKT4+ and OKT8+ cells produced LT upon phytohemagglutinin (PHA) stimulation, but the OKT4+ T cells were the major source of LT. In contrast, Leu-11a+ cells failed to produce LT. The LT production and the proliferative response to PHA, of OKT4+ and OKT8+ cells, were inhibited by prostaglandin E2 and histamine. The LT, derived from PHA-stimulated peripheral blood lymphocytes, was purified by a procedure involving Blue-agarose, Con A-Sepharose chromatography, preparative gradient polyacrylamide gel electrophoresis and preparative sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The LT activity was recovered from SDS gel with major activity peak in the Mr 76,000 region and the minor activity peak in the Mr 24,000 region. The LT derived from 1788 lymphoblastoid cell line also showed heterogeneity on SDS gel. The activity was recovered from two peaks in the region of Mr 70,000 and 20,000.

Dinoprostone↗

Familial osteosarcoma associated with 13;14 chromosomal rearrangement.

Two prepubertal sisters of American Indian origin developed osteosarcoma at 8 and 12 years of age. This familial occurrence, tumor onset prior to puberty, unusual tumor location in one who also had short stature, and ethnic background all suggest an inborn predisposition to bone cancer rather than a chance occurrence. Rearrangements involving chromosomes #13 and #14 were found in both the surviving proband and mother. Comparison of the arm ratio and prometaphase G-banding patterns of the rearranged chromosomes suggests either deletion of band 14q11.2 or pericentric inversion (with breakpoints at 13q12 and 14q11.2) in the proband's rearranged chromosome, but not in her mother's. Her mother, who had no malignancy, had a typical Robertsonian translocation [t(13;14)(p11;q11)]. Three previously reported children with chromosomal abnormalities developed osteosarcoma at unusually young ages, younger even than in reported sibships with osteosarcoma. The most frequently detected cytogenetic abnormalities in sarcoma tumor cells involve chromosomes #13 and #14. In addition, some cases of bilateral retinoblastoma and familial unilateral retinoblastoma, which are known to be at increased risk for osteosarcoma, are associated with tiny deletions on chromosome #13. Thus, there may be a causal relationship between constitutional loss or rearrangement of genetic material at these breakpoints on chromosomes #13 or #14 and development of osteosarcoma in this family that is similar to that seen in patients with small constitutional chromosomal deletions who develop Wilms' tumor and retinoblastoma.

Adolescent↗

Teratological assessment of methanol and ethanol at high inhalation levels in rats.

Alcohols are widely used as industrial solvents. In spite of the fact that ethanol is a human teratogen, there has not been systematic investigation of the potential teratogenic effects of other alcohols, particularly using the inhalation route of exposure, as would be appropriate in assessing occupational and environmental types of experience. As part of a large teratological examination of industrial alcohols, methanol and ethanol were administered by inhalation to groups of approximately 15 pregnant Sprague-Dawley rats. Methanol was administered at 20,000 ppm (20ME), 10,000 ppm (10ME), 5000 ppm (5ME), and 0 ppm (MECO) for 7 hr/day on Days 1-19 of gestation (Days 7-15 for 20ME). Ethanol was administered at 20,000 ppm (20ET), 16,000 ppm (16ET), 10,000 ppm (10ET), and 0 ppm (ETCO) for 7 hr/day on Days 1-19 of gestation. Dams were sacrificed on Day 20 (sperm = Day 0). One-half of the fetuses were examined using the Wilson technique for visceral defects, and the other half were examined for skeletal defects. The highest concentration of methanol (20ME) produced slight maternal toxicity and a high incidence of congenital malformations (p less than 0.001), predominantly extra or rudimentary cervical ribs and urinary or cardiovascular defects. Similar malformations were seen in the 10ME group, but the incidence was not significantly different from controls. No adverse effects were noted in the 5ME group. Dams in the 20ET group were narcotized by the end of exposure, and maternal weight gain and feed intake were decreased during the first week of exposure. The 16ET dams had slightly depressed weight gain (p less than 0.01) during the first week of exposure, but there were no significant effects on feed consumption. There was no definite increase in malformations at any level of ethanol, although the incidence in the 20ET group was of borderline significance.

Abnormalities, Drug-Induced↗

Prosthetic materials and muscle flaps in the repair of extensive diaphragmatic defects: an experimental study.

Relative merits of three methods of diaphragmatic hernia repair were evaluated in growing animals. Twenty-five puppies underwent laparotomy. In four controls, the left hemidiaphragm was incised and sutured primarily. In the remaining dogs, it was partially resected sparing the phrenic nerve. The defects were repaired in six with silastic sheeting, in eight with polytetrafluoroethylene (PTFE; trademark, Gore-Tex), and in seven with a thoracoabdominal muscle flap. Dogs were killed at 1, 4, and 7 months for gross and microscopic evaluation of the repair. Diaphragmatic function was evaluated by inspiratory force against a closed airway and by selective phrenic nerve stimulation (PNS). Serial fluoroscopy was used to evaluate diaphragmatic motion. Grossly the diaphragms in all groups showed compensatory growth. Microscopically the silastic was encapsulated without adherence, while PTFE showed tissue ingrowth. Maximal inspiratory force was equivalent in all groups but selective PNS revealed left-sided impairment in all experimental groups. Fluoroscopy showed paradoxical motion of the diaphragm in the muscle flap group for 1 to 2 months, and in the silastic repair group for 2 to 3 weeks, with near normal motion in the PTFE group for the entire postoperative period. These differences disappeared by 6 months. Prosthetic materials or muscle flaps are all safe for repair of large diaphragmatic hernias. Diaphragmatic growth occurs and the prosthesis remains in place. Physiologic impairment is minimal and not of clinical importance. Use of PTFE may be the preferred method as it develops better tissue incorporation and results in more normal diaphragmatic motion in the critical early postoperative period.

Animals↗

Subchronic inhalation toxicity of isobutyl nitrite in BALB/c mice. I. Systemic toxicity.

The effects of subchronic inhalation exposure to isobutyl nitrite (IBN) on body weight, selected organ weights, hematology, and gross pathology and histopathology of BALB/c mice were evaluated. Mice of both sexes were exposed at 0, 20, 50, or 300 ppm IBN for 6.5 h/d, 5 d/wk for up to 18 wk. Most changes in measured indices occurred in mice exposed at 300 ppm IBN and included decreased thymus weight (females); decreased liver weight (males); decreased white blood cell counts (males); mild focal hyperplasia and vacuolization of the epithelium lining bronchi and bronchioles of the lungs (males and females). Organ weight and hematologic changes, however, were not accompanied by any observed histologic changes. In addition, elevated methemoglobin concentrations were detected in mice of both sexes exposed at 50 and 300 ppm IBN. Body weights were not adversely affected by exposure. These data suggest that mild tissue injury, restricted to the lung, and methemoglobinemia are the major toxic effects observed following exposures of mice to IBN at concentrations up to 300 ppm for 18 wk. No treatment-related effects were noted in mice exposed at 20 or 50 ppm IBN, except for slight elevations in methemoglobin concentrations in mice exposed at 50 ppm.

Animals↗

Dependence of electrostatic diffusion of Rn progeny on environmental parameters.

In previous work it was established that electrostatic diffusion of Rn progeny attached to aerosols can be used for passive dosimetry by replacing the pump-filter assembly in an active dosimeter by an electret. In the present work, results are presented on the dependence of activity collected by an electret on aerosol concentration, aerosol diameter, attachment rate of Rn progeny to aerosols, unattached fraction of Rn progeny, and Rn progeny concentrations. The electrostatic flow rate of Rn progeny is defined and all relationships analyzed in terms of this flow rate. The electrostatic flow rate is found to be reasonably constant for 0.03 micron less than particle diameter less than 0.09 micron, unattached fraction of 218Po less than 0.40 and 70,000/cm3 less than aerosol concentration less than 180,000/cm3; experimentally obtained data outside these limits are too few to draw any definite conclusions. The results are useful from a practical point of view because typical U mine conditions are described by these limits.

Aerosols↗

The application of electrets to passive Rn progeny dosimeters.

The theoretical and experimental bases are presented for development of a passive electret dosimeter for Rn progeny. The mechanism of aerosol collection is described, and experiments to develop a suitable aerosol collecting element (electret) for a passive Rn progeny dosimeter are reported.

Air Pollutants↗

Spinal tuberculosis revisited.

Although the incidence of tuberculosis is decreasing, spinal tuberculosis is still an important disease. Delay in diagnosis and treatment results in long-term disability. We reviewed our cases of spinal tuberculosis diagnosed between 1975 and 1982, with special reference to those features that permit early diagnosis. Among the nine cases diagnosed, roentgenographic evidence of pulmonary tuberculosis (7/9) and positive PPD test (8/8) were found to be highly suggestive diagnostic clues. Computerized tomography (CT) of the spine was a useful way of determining the extent of the disease and following response to therapy. Various modes of therapy were used, and the outcome was related to the extent of the disease and duration of symptoms before initiation of therapy. In early stages, medical therapy alone is adequate; surgical intervention is necessary in cases with neurologic features.

Adult↗

Effects of fasting and refeeding on the activity of hepatic glucose-6-phosphatase in rats.

The activities of glucose-6-phosphate hydrolase and glucose-6-phosphate translocase were determined in rats fasted for 1-3 days and in animals fasted for one day and then either refed with mixed pellet or given oral or intraperitoneal glucose. The assay was based on the colorimetric measurement of the released inorganic phosphate. Fasting over 24 h significantly increased both the translocase and the hydrolase activity of glucose-6-phosphatase. These parameters showed a further increase when rats were fasted for another 24 h. In animals fasted for 24 h and then refed with standardized pellet diet, a progressive fall of enzyme activity was noticed. However, even 72 h of refeeding did not lead to complete normalization. Glucose given orally or intraperitoneally also suppressed the enzyme activity, although the effect was somewhat delayed. As expected, in fasting rats glucose and insulin levels were significantly decreased. Normoglycaemia was established after just 24 h, regardless of refeeding with pellets or with glucose. The former group exhibited hyper- and the latter hypo-insulinaemic pattern. We speculate that augmented activity of hepatic glucose-6-phosphatase during fasting stimulates the metabolism of glucose through the glucose cycle and is thereby at least partially responsible for insulin resistance accompanying the fasting state.

Administration, Oral↗

Oblique hilar tomography, computed tomography, and mediastinoscopy for prethoracotomy staging of bronchogenic carcinoma.

Preoperative oblique hilar tomography was used to evaluate hilar lymph nodes in 150 patients with clinically resectable bronchogenic carcinoma. CT was also used in the evaluation of mediastinal lymph nodes in 50 of these patients. Subsequently, all patients underwent mediastinoscopy and/or thoracotomy. Hilar and mediastinal nodes were evaluated for the presence of metastasis, and these findings were then correlated with the radiographic findings of oblique hilar tomography and CT. CT was found to be a reliable method for prethoracotomy staging of bronchogenic carcinoma and for selecting patients for mediastinoscopy. The sensitivity of CT for evaluation of mediastinal nodal metastasis was 83% and the specificity was 90%. Thus patients with negative mediastinal CT need not undergo mediastinoscopy prior to thoracotomy, while mediastinoscopy and biopsy should be done in patients with enlarged mediastinal nodes on CT. Oblique hilar tomography is an accurate method for evaluation of hilar adenopathy and for predicting mediastinal involvement by extrapolation.

Adult↗

Demyelinating encephalopathy in Lyme disease.

A 38-year-old man from southeastern Connecticut developed a diffuse encephalopathy with partial complex seizures, followed weeks later by arthritis, cryoglobulinemia, and increased serum IgM. CT showed confluent low-density lesions in the deep cerebral white matter consistent with demyelination. Neither the encephalopathy nor the CT abnormalities improved. Lyme disease was diagnosed serologically 4 years later.

Adult↗